Preparation of a pulmonary surfactant for instillation and oral application

ABSTRACT

A pulmonary surfactant formulation for instillation and oral application, containing at least 0.1% by weight of 2,3 -dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone in addition to an effective amount of pulmonary surfactant and usual excipients.

This application is a 371 of PCT/EP98/00745 filed Feb. 11, 1998.

Pulmonary surfactant is a complex of phospholipids, neutral lipids andsurfactant proteins which together form a monolayered barrier betweenthe air and the liquid surface of the lung. Pulmonary surfactant isproduced in the alveolar type II cells from which it is released intothe alveolar space. Pulmonary surfactant can be obtained by extractionor recombination.

To date, pulmonary surfactant has been employed for instillation indiseases or deficiencies of the lung, especially in IRDS, therespiratory distress syndrome in children, and in ARDS.

It has now been found that also for the oral treatment of diseases ofthe entire digestive tract (mouth, esophagus, stomach and intestine),the effectiveness and the shelf life of pulmonary surfactant can beincreased by an addition of at least 0.1% by weight of2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone.

2,3-Dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone is also known bythe designation of coenzyme Q10. This substance plays a role in therespiratory chain and, in addition, is an antioxidant which is capableof scavenging free radicals, which are transmitted by vitamins, inparticular. In addition, Q10 determines the elasticity and dynamics ofcell membranes. Therefore, it has been recommended as a monopreparationand in combination with other active substances for oral administration.Further, it is offered for skin care in the form of a liposome creamwhich allows the active ingredient to penetrate through the horny layerbarriers and then to accumulate in the various strata of the skin.However, this does not provide any indication of that even small amountsof this substance are capable of stabilizing the active substance,pulmonary surfactant, and enhancing its effectiveness. In particular,higher amounts of the active substance2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone are capable, wheninstilled into the lung, of strengthening the lung-resident immunesystem, of helping the cell to regenerate damaged cellular structures,and of simultaneously enhancing the effectiveness of pulmonarysurfactant.

It is surprising thet Q10 provides dynamics not only to the lipidbilayers, but also to the pulmonary surfactant system.

Thus, the present invention relates to pulmonary surfactant formulationsfor instillation containing at least 0.1% by weight of2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone in addition to aneffective amount of pulmonary surfactant and usual excipients.

The amount of 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone maybe increased to a weight ratio of 1:1 with the pulmonary surfactant,whereby special therapeutic effects are achieved.

What is claimed is:
 1. A pulmonary surfactant formulation comprisingeffective amounts of2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone and pulmonarysurfactant.
 2. A formulation of claim 1, wherein effective amounts of2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone and pulmonarysurfactant are in the weight ratio from 0.1:1 to 1:1.
 3. A formulationof claim 2, in a form to be administered orally.
 4. A formulation ofclaim 2, suitable for instillation.
 5. A formulation of claim 1, in aform to be administered orally.
 6. A formulation of claim 1, suitablefor instillation.
 7. A formulation of claim 1, further comprisingexcipients.
 8. A formulation of claim 2, further comprising excipients.9. A formulation of claim 3, further comprising excipients.
 10. Aformulation of claim 4, further comprising excipients.
 11. A formulationof claim 5, further comprising excipients.
 12. A formulation of claim 6,further comprising excipients.